scholarly journals Amelioration of Cigarette Smoke-Induced Mucus Hypersecretion and Viscosity by Dendrobium officinale Polysaccharides In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rui Chen ◽  
Yingmin Liang ◽  
Mary Sau Man Ip ◽  
Kalin Yanbo Zhang ◽  
Judith Choi Wo Mak
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Secretory Granules ◽  
Dendrobium Officinale ◽  
In Vivo Models ◽  
Mucus Hypersecretion ◽  
Mucin Gene ◽  
Starting Point

Chronic obstructive pulmonary disease (COPD), characterized by oxidative stress and inflammation, is one of the leading causes of death worldwide, in which cigarette smoke (CS) is the major risk factor. Dendrobium officinale polysaccharides (DOPs) are the main active ingredients extracted from Dendrobium officinale, which have been reported to have antioxidant and anti-inflammatory activity as well as inhibition of mucin gene expression. This study is aimed at investigating the effect of DOPs on CS-induced mucus hypersecretion and viscosity in vitro and in vivo. For in vitro study, primary normal human bronchial epithelial cells (HBECs) differentiated at the air-liquid interface (ALI) culture for 28 days were stimulated with cigarette smoke medium (CSM) in the absence or presence of various concentrations of DOPs or N-acetylcysteine (NAC) for 24 hours. For in vivo study, male Sprague-Dawley rats were randomized to sham air (SA) as control group or CS group for 56 days. At day 29, rats were subdivided and given water as control, DOPs, or NAC as positive control as a mucolytic drug via oral gavage for the remaining duration. Samples collected from apical washing, cell lysates, bronchoalveolar lavage (BAL), and lung tissues were evaluated for mucin gene expression, mucus secretion, and viscosity. DOPs ameliorated the CS-induced mucus hypersecretion and viscosity as shown by the downregulation of MUC5AC mRNA, MUC5AC secretary protein, and mucus viscosity via inhibition of mucus secretory granules in both in vitro and in vivo models. DOPs produced its effective effects on the CS-induced mucus hypersecretion and viscosity via the inhibition of the mucus secretory granules. These findings could be a starting point for considering the potential role of DOPs in the management of the smoking-mediated COPD. However, further research is needed.

scholarly journals Differential Regulation of β-Defensin Gene Expression during Cryptosporidium parvum Infection

2004 ◽  
Vol 72 (5) ◽  
pp. 2772-2779 ◽  
Author(s):  
Tarek K. Zaalouk ◽  
Mona Bajaj-Elliott ◽  
John T. George ◽  
Vincent McDonald
Keyword(s):  
Gene Expression ◽  
Cryptosporidium Parvum ◽  
Protozoan Parasite ◽  
Immune Defense ◽  
Microbial Pathogens ◽  
In Vivo Models ◽  
Defensin Gene ◽  
Intestinal Epithelia

ABSTRACT Invasion of enterocytes by pathogenic microbes evokes both innate and adaptive immune responses, and microbial pathogens have developed strategies to overcome the initial host immune defense. β-Defensins are potentially important endogenous antibiotic-like effectors of innate immunity expressed by intestinal epithelia. In this study, the interplay between the enteric protozoan parasite Cryptosporidium parvum and host epithelial β-defensin expression was investigated. Using human and murine models of infection, we demonstrated that C. parvum infection differentially regulates β-defensin gene expression. Downregulation of murine β-defensin-1 mRNA and protein was observed in both in vitro and in vivo models of infection. Infection of the human colonic HT29 cell line with the parasite resulted in differential effects on various members of the defensin gene family. Partial reduction in human β-defensin-1 (hBD-1), induction of hBD-2, and no effect on hBD-3 gene expression was observed. Recombinant hBD-1 and hBD-2 peptides exhibited significant antimicrobial activity against C. parvum sporozoites in vitro. These findings demonstrate that C. parvum infection of enterocytes may affect the expression of various defensins in different ways and suggest that the overall outcome of the effect of antimicrobial peptides on early survival of the parasite may be complex.

Microfluidic neural axon diode

TECHNOLOGY ◽  
2016 ◽  
Vol 04 (04) ◽  
pp. 240-248 ◽  
Author(s):  
Sangcheol Na ◽  
Myeongwoo Kang ◽  
Seokyoung Bang ◽  
Daehun Park ◽  
Jinhyun Kim ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Axon Growth ◽  
In Vivo Models ◽  
Starting Point ◽  
Wide Range ◽  
Reproducible Method ◽  
Physical And Chemical ◽  
Biology Research

Neural circuits, groups of neurons connected in directional manner, play a central role in information processing. Advances in neuronal biology research is limited by a lack of appropriate in vitro methods to construct and probe neuronal networks. Here, we describe a microfluidic culture platform that directs the growth of axons using “neural diode” structures to control neural connectivity. This platform is compatible with live cell imaging and can be used to (i) form pre-synaptic and postsynaptic neurons by directional axon growth and (ii) localize physical and chemical treatment to pre- or postsynaptic neuron groups (i.e. virus infection and etc.). The “neural diode” design consist of a microchannel that split into two branches: one is directed straight toward while the other returns back toward the starting point in a closed loop to send the axons back to the origin. We optimized the “neural diode” pattern dimension and design to achieve close to 70% directionality with a single unit of the “diode”. When repeated 3 times, near perfect (98–100% at wide range of cell concentrations) directionality can be achieved. The living neural circuit was characterized using Ca imaging and confirmed their function. The platform also serves as a straightforward, reproducible method to recapitulate a variety of neural circuit in vitro that were previously observable only in brain slice or in vivo models. The microfluidic neural diode may lead to better models for understanding the neural circuit and neurodegenerative diseases.

Thyroid Hormone Regulates Endogenous Amyloid-β Precursor Protein Gene Expression and Processing in Both In Vitro and In Vivo Models

Thyroid ◽  
2006 ◽  
Vol 16 (12) ◽  
pp. 1207-1213 ◽  
Author(s):  
Stephen A. O'Barr ◽  
Jin S. Oh ◽  
Chan Ma ◽  
Gregory A. Brent ◽  
James J. Schultz
Keyword(s):  
Gene Expression ◽  
Thyroid Hormone ◽  
Protein Gene ◽  
Amyloid Β ◽  
Precursor Protein ◽  
In Vivo Models

scholarly journals AB0158 IMPACT OF JAK INHIBITORS ON MACROPHAGE POLARISATION: PERSPECTIVES FOR SYSTEMIC SCLEROSIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1380.3-1380
Author(s):  
A. Lescoat ◽  
A. Ballerie ◽  
M. Lelong ◽  
C. Morzadec ◽  
S. Jouneau ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Sclerosis ◽  
Blood Monocytes ◽  
Jak Inhibitors ◽  
In Vivo Models ◽  
Macrophage Polarisation ◽  
Healthy Donors ◽  
The Impact

Background:Macrophage can adopt various phenotypes and activation states according to their surrounding microenvironment. M1 or inflammatory macrophages are generated under IFNɣ/LPS signaling and express the membrane marker CD86. Different subtypes of M2 macrophages are also described: M2a macrophages (generated under IL4/IL13 signaling) and characterized by a high expression of CD206 and pro-fibrotic properties and, M2c macrophages (generated under IL10 and/or glucorticoid signaling), considered as anti-inflammatory resolving macrophages. There is growing interest in the role of macrophages in the pathogenesis of Systemic Sclerosis (SSc). Recent studies highlight that macrophages from fibrotic tissues such as lung or skin from SSc patients have a M2 phenotype whereas, in blood-monocytes derived macrophages (MDM), SSc MDM have a mixed signature associating M1 and M2 characteristics. Jak inhibitors are treatments used in rheumatoid arthritis and that can variously target signals that could be involved both in M1 and in M2 polarisation.Objectives:This study evaluates the impact of three Jak inhibitors on the polarisation state of human MDM in vitro.Methods:Blood monocytes form healthy donors (HD) were differentiated with M-CSF (for 7 days) in MDM and pre-treated by ruxolitinib (Jak2-Jak1 inhibitor), tofacitinib (Jak3 inhibitor) or itacitinib (Jak1 inhibitor) (1µM for all). They were then polarised into M1i (IFNɣ, 20µg/mL), M1Li (IFNɣ+LPS, 20µg/mL), M2a (IL4+IL13; 20µg/ML), M2c (IL10, 20µg/mL) and M2c(dex) (IL10+dexamethasone, 10 nM). The impact of each Jak inhibitor on phenotype (flow cytometry), gene expression (qPCR) and cytokine secretion (ELISA) was evaluated in each polarisation state.Results:Concerning phenotypes, all Jak inhibitors reduced the expression of the M1i and M1Li marker CD86, but ruxolitinib had a higher effect. Only ruxolitinib reduced the expression of the M1i marker MHCII. All Jak inhibitors reduced the expression of CD206 in M2a. They had no impact on the expression of CD163, CD204 in any M2 conditions. Key M1 genes were repressed by all Jak inhibitors, such as CXCL10, IL6 or TNFα with a more significant effect of ruxolitinib. All Jak inhibitors reduced the gene expression of CXCL13 and SOCS3 in M2c. Secretion levels of IL6 and CCL18 were also repressed, with a more significant effect of ruxolitinib.Conclusion:Jak inhibitors can limit M1 and M2 polarisation state in vitro, with a more significant effect of the Jak2-Jak1 inhibitor ruxolitinib. The relevance of these results in MDM from SSc patients and in vivo models of SSc is still to be determined.Disclosure of Interests:Alain LESCOAT: None declared, Alice Ballerie: None declared, Marie Lelong: None declared, Claudie Morzadec: None declared, Stéphane Jouneau Grant/research support from: AIRB, Boehringer Ingelheim, LVL Medical, Novartis, Roche, Bellorophon Therapeutics, Biogen, Fibrogen, Galecto Biotech, Gilead Sciences, Pharm-Olam, Pliant Therapeutics, Savara Pharmaceuticals/Serendex Pharmaceuticals, Consultant of: Actelion, AIRB, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GlazoSmithKline, LVL Medical, Mundipharma, Novartis, Pfizer, Roche, Sanofi, Patrick Jégo: None declared, Laurent Vernhet: None declared, Olivier Fardel: None declared, Valérie Lecureur: None declared

scholarly journals Shigella dysenteriae Modulates BMP Pathway to Induce Mucin Gene Expression In Vivo and In Vitro

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e111408 ◽  
Author(s):  
Ashidha Gopal ◽  
Soumya Chidambaram Iyer ◽  
Udhayakumar Gopal ◽  
Niranjali Devaraj ◽  
Devaraj Halagowder
Keyword(s):  
Gene Expression ◽  
Shigella Dysenteriae ◽  
Mucin Gene ◽  
Bmp Pathway

Biomodelling Angiogenesis

2016 ◽  
Vol 7 (2) ◽  
pp. 127-134
Author(s):  
Nikolai A Verlov ◽  
Alexander P Trashkov ◽  
Maria A Pahomova ◽  
Nikolai V Haitsev ◽  
Evgeni I Malyshev
Keyword(s):  
Wide Spectrum ◽  
Circulation System ◽  
Human Beings ◽  
In Vivo Models ◽  
Normal Tissues ◽  
Starting Point ◽  
Golden Standard ◽  
Inducing Factors

Success or failure of studies in various areas of biology depend on the presence or absence of convenient and effective adequate models of pathologic processes with fair predictability. In spite of variability of models used in contemporary angiology neither of them can be considered to be “golden standard” or etalon for elaborating new methods targeted at blood vessels. The need for a score of different models for studies of each stage of angiogenesis is one of major difficulties in forming a universal concept describing angiogenesis in humans and animals. A hypothesis of malignant neoplasma growth inhibition by means of blocking angiogenesis inducing factors, their receptors or direct destruction of microvessels’ wall is a starting point for profound angiogenesis studies using various in vitro and in vivo models. A wide spectrum of oncogenesis models allows to scrutinize it from various angles revealing general principles of neoplasma development, mechanisms of its interaction with normal tissues and organs, including the circulation system. Using transgenic с animals helped to disclose the key role of angiogenesis in the development of the organism as well as get results maximally close to the effects characteristic of studies of various aspects of angiogenesis in human beings.

Oxygen modulates alpha 1B-adrenergic receptor gene expression by arterial but not venous vascular smooth muscle

1996 ◽  
Vol 271 (4) ◽  
pp. H1599-H1608 ◽  
Author(s):  
A. D. Eckhart ◽  
Z. Zhu ◽  
W. J. Arendshorst ◽  
J. E. Faber
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
In Vivo Models ◽  
Beta Actin ◽  
Actin Mrna ◽  
Alpha Actin

Blood and tissue O2 levels are major determinants of short-term autoregulatory adjustments in vascular smooth muscle cell (SMC) tension and may effect long-term alterations in SMC catecholamine responsiveness. We examined the hypothesis that prolonged hypoxia altered gene expression of alpha 1-adrenoceptors. After exposure of cultured aortic (in vitro) SMC to 3% O2 for 8 h, alpha 1B mRNA increased to 523% (P = 0.02) of control cells (21% O2) and to 205% (P = 0.04) in in situ organ-cultured aortic SMC. In vivo hypoxic hypoxia (10% inspired O2) similarly increased aortic SMC alpha 1B mRNA 180% (P = 0.02). In contrast, alpha 1D, alpha-actin and beta-actin mRNA levels were not changed in aortic SMC by low O2 in the in vitro, in situ, or in vivo models. Unlike aortic SMC, vena caval SMC alpha 1B mRNA expression did not change with low-O2 exposure in vitro or in vivo, nor did alpha 1D, alpha-actin or beta-actin mRNA. Aortic SMC alpha 1B transcription rate increased 360% (P = 0.02), whereas alpha 1D, alpha-actin, and beta-actin transcription was unchanged. Neither alpha 1B nor alpha 1D mRNA stability was altered by low-O2 exposure. Total alpha 1-adrenoceptor density ([3H]prazosin binding) increased 12% (P = 0.04) after 24 h of 3% O2. This was associated with a 200% increase (P < 0.01) in the chloroethylclonidine (CEC)-sensitive alpha 1-adrenoceptor population and no change in CEC-insensitive alpha 1-adrenoceptor density. Exposure of aortic SMC to 24 h of 3% O2 increased the maximum response of norepinephrine-evoked elevations in intracellular Ca2+ as measured using fura 2. Low O2 did not change responses to another G protein-coupled receptor, angiotensin II. These data suggest that reduced O2, during prolonged hypoxemia or tissue ischemia, may selectively increase expression of functionally coupled alpha 1B-adrenoceptors in arterial blood vessels.

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